Rosiglitazone inhibits bone regeneration and causes significant accumulation of fat at sites of new bone formation.

Liu L, Aronson J, Huang S, Lu Y, Czernik P, Rahman S, Kolli V, Suva LJ, Lecka-Czernik B.

Arkansas Children's Hospital Research Institute, University of Arkansas for

Medical Sciences, Little Rock, AR, USA.


Thiazolidinediones (TZDs), peroxisome proliferator-activated receptor gamma activators, and insulin sensitizers represent drugs used to treat hyperglycemia in diabetic patients. Type 2 diabetes mellitus (T2DM) is associated with a twofold increase in fracture risk, and TZDs use increases this risk by an additional twofold. In this study, we analyzed the effect of systemic administration of the TZD rosiglitazone on new bone formation in two in vivo models of bone repair, a model of drilled bone defect regeneration (BDR) and distraction osteogenesis (DO) and a model of extended bone formation. Rosiglitazone significantly inhibited new endosteal bone formation in both models. This effect was correlated with a significant accumulation of fat cells, specifically at sites of bone regeneration. The diminished bone regeneration in the DO model in rosiglitazone-treated animals was associated with a significant decrease in cell proliferation measured by the number of cells expressing proliferating cell nuclear antigen and neovascularization measured by both the number of vascular sinusoids and the number of cells producing proangiogenic vascular endothelial growth factor at the DO site. In summary, rosiglitazone decreased new bone formation in both BDR and DO models of bone repair by mechanisms which include both intrinsic changes in mesenchymal stem cell proliferation and differentiation and changes in the local environment supporting angiogenesis and new bone formation. These studies suggest that bone regeneration may be significantly compromised in T2DM patients on TZD therapy.

Muscle strength and body composition are clinical indicators of osteoporosis.

Rikkonen T, Sirola J, Salovaara K, Tuppurainen M, Jurvelin JS, Honkanen R, Kröger H.

Bone and Cartilage Research Unit, Mediteknia Building, University of Eastern Finland, Kuopio, Finland, Questo indirizzo email è protetto dagli spambots. E' necessario abilitare JavaScript per vederlo. .


We examined the role of muscle strength, lean tissue distribution, and overall body composition as indicators of osteoporosis (OP) in a pooled sample of 979 Finnish postmenopausal women (mean age 68.1 years) from the Kuopio Osteoporosis Risk Factor and Prevention study. Bone mineral density (BMD) at the femoral neck (FN) and total body composition were assessed by dual-energy X-ray absorptiometry scans. The women (n = 979) were divided into three groups according to WHO criteria, based on FN BMD T score: normal (n = 474), osteopenia (n = 468), and OP (n = 37). Soft tissue proportions, fat mass index (FMI, fat/height²), lean mass index (LMI, lean/height²), and appendicular skeletal muscle mass (ASM, (arms + legs)/height²) were calculated. Handgrip and knee extension strength measurements were made. OP subjects had significantly smaller LMI (p = 0.001), ASM (p = 0.001), grip strength (p < 0.0001), and knee extension strength (p < 0.05) but not FMI (p > 0.05) compared to other subjects. Grip and knee extension strength were 19 and 16 % weaker in OP women compared to others, respectively. The area under the receiver operating characteristic curve was 69 % for grip and 71 % for knee extension strength. In tissue proportions only LMI showed predictive power (63 %, p = 0.016). An overall linear association of LMI (R (2) = 0.007, p = 0.01) and FMI (R (2) = 0.028, p < 0.001) with FN BMD remained significant. In the multivariate model, after adjusting for age, grip strength, leg extension strength, FMI, LMI, number of medications, alcohol consumption, current smoking, dietary calcium intake, and hormone therapy, grip strength (adjusted OR = 0.899, 95 % CI 0.84-0.97, p < 0.01), leg extension strength (OR = 0.998, 95 % CI 0.99-1, p < 0.05), and years of hormone therapy (OR = 0.905, 95 % CI 0.82-1, p < 0.05) remained as significant determinants of OP. Muscle strength tests, especially grip strength, serve as an independent and useful tool for postmenopausal OP risk assessment. In addition, lean mass contributes to OP in this age group. Muscle strength and lean mass should be considered separately since both are independently associated with postmenopausal BMD.

Impaired bone health in inflammatory bowel disease: a case-control study in 80 pediatric patients.

Laakso S, Valta H, Verkasalo M, Toiviainen-Salo S, Viljakainen H, Mäkitie O.

Children's Hospital, Helsinki University Central Hospital and University of Helsinki, P.O. Box 281, 00029, Helsinki, Finland, Questo indirizzo email è protetto dagli spambots. E' necessario abilitare JavaScript per vederlo. .


Previous studies have indicated that children with inflammatory bowel disease (IBD) may not achieve optimal bone mass. We evaluated the skeletal characteristics in children and adolescents with IBD. This cross-sectional cohort study comprised 80 IBD patients (median age 14.9 years, range 5-20) with a median disease duration of 3.4 years; 51 had ulcerative colitis, 26 Crohn disease, and 3 unspecified colitis. Eighty age- and gender-matched healthy subjects served as controls. Areal bone mineral density (aBMD), body composition, and vertebral fractures (VFs) were assessed by DXA. Bone age (BA) was determined for IBD patients. Findings were correlated with disease- and treatment-related parameters and biochemistry. IBD patients had lower BA-adjusted lumbar spine and whole-body aBMD (p < 0.001 for both) and whole-body BMC adjusted for height (p = 0.02) than controls. Lean mass and fat mass Z scores did not differ between the groups, but IBD patients had lower whole-body BMC relative to muscle mass (p = 0.006). Despite vitamin D supplementation in 48 %, vitamin D deficiency was common. In IBD cumulative weight-adjusted prednisolone dose >150 mg/kg for the preceding 3 years increased the risk for low whole-body aBMD (OR = 5.5, 95 % CI 1.3-23.3, p = 0.02). VFs were found in 11 % of patients and in 3 % of controls (p = 0.02). IBD in childhood was associated with low aBMD and reduced bone mass accrual relative to muscle mass; the risk for subclinical VFs may be increased. These observations warrant careful follow-up and active preventive measures.